SYNTHESIS OF AMINO ACID-DERIVED NATURAL PRODUCTS

氨基酸衍生天然产物的合成

• 批准号: 3282910
• 负责人: David A Evans
• 金额: $ 23.05万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-08-01 至 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3282910
• 关键词: alkaloids; aminoacid biosynthesis; animal poison; antileukemic agent; antineoplastic antibiotics; antineoplastics; beta lactam antibiotic; colchicine; drug design /synthesis /production; indoles; neurotoxins; quinones; tryptophan

The overriding objectives of this proposal are to make creative contributions to the total synthesis of naturally occurring substances possessing clinically significant biological activity. The principal classes of structures which will be the focal point for both new reaction methodology and the subject of synthesis activities are largely derived from amino acids. Targets for total synthesis will include the Beta-lactam antibiotics thienamycin, northienamycin, PS-5 and related carbapenems. Two fundamentally different general approaches to the asymmetric synthesis of the Beta-lactam nucleus will be investigated. Other targets for total synthesis will include the powerful antineoplastic agents, saframycin, macbecin, herbimycin, bouvardin, deoxybouvardin, and patellamides A-C. Related targets for total synthesis will include the complex peptide antibiotics of the vancomycin class. Specific objectives within this family include vancomycin, teicoplanin, and restocetin. The major thrust in new reaction methodology which will accompany these target-oriented projects will be the development of new approaches to the asymmetric synthesis of Alpha-amino acids. Within the context of this objective, a number of complementary concepts are outlined. For example, amino acid syntheses based upon the development of chiral glycine enolate synthons, chiral electrophilic aminating agents, and chiral metal nitrenoids are presented.

该提案的首要目标是发挥创意 对天然物质全合成的贡献 具有临床意义的生物活性。 校长 结构类别将成为新反应的焦点 合成活动的方法论和主题很大程度上源自 来自氨基酸。 全合成的目标将包括β-内酰胺 抗生素硫霉素、诺替那霉素、PS-5和相关碳青霉烯类。 二 不对称合成的根本不同的一般方法 将研究β-内酰胺核。 其他目标总计 合成将包括强大的抗肿瘤药物，沙弗霉素， 麦克菌素、除草霉素、布瓦尔丁、脱氧布瓦尔丁和帕特拉酰胺 A-C。 全合成的相关目标将包括复杂的肽 万古霉素类抗生素。 在此范围内的具体目标 家族包括万古霉素、替考拉宁和瑞斯托菌素。 主要推力 新的反应方法将伴随这些目标导向 项目将开发解决不对称问题的新方法 α-氨基酸的合成。 在此目标的背景下， 概述了许多互补的概念。 例如，氨基酸 基于手性甘氨酸烯醇化物合成子开发的合成， 手性亲电胺化剂和手性金属氮化物是 提出。